The eye is a complex system of highly differentiated tissues of various developmental origins. Many genes essential for eye function are tissue-specific and many of those known are associated with genetic eye diseases. The majority of human expressed genes are known only through expressed sequence tags (ESTs). Since eye tissues were poorly represented in the cDNA libraries initially contributed to dbEST a project called NEIBank was begun to improve the EST coverage and to develop a molecular encyclopedia for the eye. cDNA libraries for several human eye tissues, including lens, iris, RPE/choroid, retina, trabecular meshwork, lacrimal gland and keratoconus cornea have been constructed and examined by in-depth sequencing. Between 2,000 and 10,000 clones from each un-normalized library have been sequenced, analyzed and clustered using custom software, GRIST. Several libraries have been made for important animal models, including angle, retina and whole eye of rat, whole eye, lacrimal gland, retina and RPE of mouse, anterior and posterior segments for dog and rabbit and lens and whole eye for zebrafish . Many novel genes and genetic variants have been identified. In total, approximately 40,000 ocular cDNA clones have been sequenced and organized in a web-based database (http://neibank.nei.nih.gov) that contains keyword and chromosomal location data. The human DNA resource generated by this work have been used to create micro-arrays for ocular studies. A cDNA microarray with over 13,000 non-redundant human eye expressed sequences has been constructed and is being tested. Several novel genes discovered through NEIBank have been selected for verification and further study. These include lengsin an abundant novel lens specific transcript related to glutamine synthetase and iris-expressed growth factor. Lengsin expression is associated with terminal differentiation and nuclear breakdown in the lens. Recombinant mouse and human proteins are being used for function and structure studies and transgenic mice using the lengsin promoter have been made. A knock-mouse model for lengsin is under construction using "recombineering" technology. We have shown that IEGF/PDGFD has a key role in control of lens growth and development of the anterior segment. Antibody to IEGF blocks lens cell proliferation and may have translational research applications in secondary and subcapsular cataracts. This factor is also specifically expressed in the retina and may have a role in photoreceptor health. Analysis of a new keratoconus cornea library has shown that the library contains an excellent representation of human cornea expressed genes but has also revealed an important candidate gene for involvement in this condition. The leads from these data are being pursued, along with several other novel gene products including retbindin and Mp19ins. Retbindin may be the carotenoid binding protein of the retina, while Mp19ins may have a specific role in correct formation of the human lens.